Endocrine Abstracts

Introduction: Ectopic ACTH syndromes account for 5–10% of Cushing syndrome, with intrathoracic and gastrointestinal–pancreatic neuroendocrine tumors being the most common causes, followed by small cell lung cancer, adrenal paraganglioma and medullary thyroid carcinoma.

Case report: A 50-year-old male hypertensive and diabetic patient was transferred to our clinic for emergency endocrine care for hypokalemia. He had mild hypercortisolism and liver metastases. We admitted a patient with normal body mass, facial and thoracic hyperemia, lower muscle weakness and a right hypochondriac sensitive normal volume abdomen, without muscular defense signs or stretch marks. Biochemistry tests revealed hypokalemia ranging between 2.5 and 3.7 mEq/l, despite the intensive treatment with potassium chloride and spironolactone, and mild hepatic cytolysis. Hormonal tests confirmed ACTH-dependent hypercortisolism (ACTH>2000 pg/ml, cortisol >63.4 mg/dl) and high NET markers-chromogranin A >900 ng/ml, neuron-specific enolase >200 μg/l, and CEA (59.18 ng/ml). The CT scan showed hyperplasia of the adrenal glands, a solid nodule of the uncinate process and multiple hepatic tumors suggesting metastases.

Ketoconazole failed to control hypercortisolism due to hepatic side effects. The patient was referred for bilateral adrenalectomy, performed in association with right hemicolectomy and ileo-transversal anastomosis, with a slightly favorable evolution afterwards, on gluco and mineralocorticoid replacement therapy with improvement of the ionogram, blood pressure and glycaemia. The histopathological exam confirmed proximal colon carcinoma-ulcerated adenocarcinoma, mucinous component (~35–40%) and large cell neuroendocrine carcinoma (~35%) suggesting a MiNEN (mixed NET and non-NET). The immunohistochemistry (IHC) exam showed positive staining for synaptophysin and chromogranin A, MMR protein (MSH2, MSH6, MLH1, PMS2), intense positive diffuse p53, CK20 and SATB2, a ki67 of 80–85%, but negative staining for ACTH.

Particularities: Despite the negative staining for ACTH, Cushing’s syndrome symptoms improved after tumor resection and adrenalectomy. A large tumor may harbor different ACTH expression in different areas, which can be the cause of ACTH negative IHC sample. The age at diagnosis was lower than the known mean age (60 years) and the symptoms onset and evolution were fulminant in this case, almost one month, despite all medical intervention.

Conclusion: Management of ectopic ACTH syndrome due to neuroendocrine tumor is complex. The gold standard is the complete surgical resection of the primary tumor. If the surgery fails, it is important to control hypercortisolemia and prevent its complications. The severity and histological pattern of the tumor is related with the ectopic ACTH syndrome prognosis.